Biodegradable materials based on native starch, (chemically) modified starch and like substances are already known in the art for a long period of time.
For example, EP A 118.240 to Warner Lambert Co., incorporated by reference herein, discloses a process for the preparation of a mouldable starch composition, wherein a starch having a molecular weight of 10,000 to 20,000,000 Dalton and a water content of 5 to 30 wt. %, based on the weight of the dry composition, is formulated. The mouldable starch composition is used for the manufacture of injection moulded products, in particular capsules. In the first step of this process, starch is extruded and melted at a temperature of 80° to 240° C. and at a pressure of 60 to 300 MPa (6×107 to 3×108 N/m2=600 to 3000 bar). In the second step of the process, the melted starch is dissolved in water at a temperature of 80° to 240° C. and at a pressure of 60 to 300 MPa. In the third step of the process, the dissolved starch is plasticized under conditions as employed in the previous step, i.e. at a temperature of 80° to 240° C. and at a pressure of 60 to 300 MPa. Optionally, the starch is mixed with a modified starch. Also optionally, the starch is mixed with additives such as a plasticizer, e.g. polyethylene glycol or glycerol, a lubricant, e.g. a lipid or a phospholipid, or an extender, e.g. gelatine. The injection moulded products, e.g. capsules, are manufactured in the fourth step of the process, wherein the plasticized starch is injected into a mould at a temperature of at least 80° C. and at a pressure of 60 to 300 MPa and a clamping force of 100 to 10,000 kN. However, mechanical properties of the injection moulded products, e.g. the capsules, are not disclosed. Furthermore, cytotoxicity and in vivo degradability properties of the mouldable starch composition are not disclosed. Additionally, as appears from later prior art, the mouldable starch composition can be characterised by the term “destructurised starch” since it is produced from starch that is subjected to a heat treatment that heats the starch to a temperature above its glass transition and melting temperatures with the result that the molecular structure of the starch is at least disordered.
EP A 282.451 of Warner Lambert Co., incorporated by reference herein, also discloses a process for the preparation of a destructurised starch, wherein the starch comprising 10-25 wt. % of water, calculated on the weight of the starch, is further mixed with an inorganic acid, e.g. HCl or H2SO4. The inorganic acid functions as a chain scission catalysts, i.e. as an agent for acidic hydrolysis, and induces breaking of α-1,4-glycosidic bonds so that a destructurised starch having a decreased molecular weight is formed, i.e. that the average molar mass of the starch is reduced by a factor of 2 to 5,000, preferably 4 to 1,000, more preferably 5 to 300. The process can conveniently be performed in an extruder at a temperature of 100° to 200° C., preferably 140° to 190° C. and most preferably 160° to 185° C. and at relatively low pressures, i.e. a pressure of 0 to 15 MPa (0 to 150×105 N/m2=0 to 150 bar), preferably 0 to 7.5 MPa and most preferably 0 to 5 MPa. The starch may be mixed with additives such as plasticizers, lubricants, extenders and the like, wherein the lubricants may be added without plasticizer or extender. Preferred lubricants are hydrogenated or hardened vegetable or animal fats, optionally in combination with mono- or diglycerides or phosphatides such as lecithin. The destructurised starch can be used to manufacture a range of shaped articles by a range of techniques. For example, thicker walled articles can be made by injection moulding the destructurised starch at a pressure of 30 to 300 MPa, preferably 70 to 220 MPa. The destructurised starch according to EP A 282.451 would be advantageous as it exhibits improved flow characteristics and improved processability which enables lower temperatures and lower pressures to be used in the injection moulding process. However, it is to be expected that shaped articles manufactured from the destructurised starch according to EP A 282.451 have a low tensile strength due to the fact that the destructurised starch has a relatively low molecular weight.
Other processes for the preparation of destructurised starch which is used for the manufacture of shaped articles are for example disclosed in EP A 298.920, GB A 2.190.093, EP A 304.401, EP A 474.705, EP 495.056, EP A 774.975 and EP A 994.564, all incorporated by reference herein.
U.S. Pat. No. 5,409,973, incorporated by reference, also discloses a process for the preparation of destructurised starch, wherein starch is extruded in the presence of up to 20 wt. % of water (this amount included the intrinsic water content of the starch employed), based on the total weight of the composition supplied to the extruder, wherein the water content is reduced to below 6 wt. % of water (cf. column 4, lines 3-17). According to the examples, the breaking stress (tensile strength) is not more than 10.0 N/mm2.
U.S. Pat. No. 5,439,953, incorporated by reference, discloses a one-step process for the preparation of polymer-modified starch materials wherein a mixture of starch, an aqueous dispersion of a synthetic polymer and optionally but preferably a plasticizer selected from the group consisting of ethylene glycol, propylene glycol, butane diol, glycerol and ethers thereof are extruded. According to the examples, the polymer-modified starch materials have a tensile strength of not more than 4.0 N/mm2.
According to EP A 298.920 of Warner Lambert Co., the starting material is treated with water and/or acid having a pH of 3 or lower to remove electrolytes and divalent cations so that the processability of the starch during the destructurising step is improved.
GB A 2.190.093 of Warner Lambert Co. discloses a process for the preparation of a destructurised starch granulate wherein a mixture of starch, a texturising agent, preferably titanium oxide, silicon dioxide or a mixture thereof, and a lubricant/release agent and/or a melt-flow accelerator are extruded. This granulate would have good flow behaviour used for the manufacture of shaped articles such as capsules by injection moulding.
EP A 304.401 of Novamont S.p.A. discloses shaped articles made from pre-processed starch and a two-step process for the preparation of destructurised starch. In the first step of this process, a composition comprising starch is extruded at a water content of 10-20 wt. %, based on the weight of the composition, at a temperature of 120° to 190° C., preferably 130° to 190° C., and a pressure within the range of the vapour pressure of water at the prevailing temperature and 15 MPa, preferably 10 MPa, more preferably 8 MPa, to form a starch granulate. This starch granulate has a water content of 10-20 wt. %, preferably 12-19 wt. %, more preferably 14-18 wt. %, based on the weight of the starch granulate. The starch granulate is then again processed in a second step in an extruder at a temperature of 80° to 200° C., preferably 120° to 190°, more preferably 140° to 180° C., and a pressure of 0 to 15 MPa, preferably 0 to 10 MPa, and most preferably 0 to 8 MPa to form a melt. The melt is subsequently transferred to a mould while the water content is kept constant and the shaped articles are then formed by cooling the melt to a temperature below the glass transition temperature of the melt. Instead of the second extrusion step, the shaped article can be manufactured by injection moulding, wherein for the injection step a pressure of 30 to 300 MPa (=30,000,000 to 300,000,000 N/m2=300 to 3000 bar), preferably 70 to 220 MPa, is employed. The shaped articles include bottles, sheets, films, packaging materials, pipes, rods, laminates, sacks, bags and pharmaceutical capsules which indicate that these shaped articles have poor biologically degradability. Tests further revealed that the two-step process according to EP A 304.401 provided shaped articles having higher extensions at break when compared with shaped articles formed in a single-step process as disclosed in e.g. EP A 118.240. Tests further showed that extensions at break of moulded test specimen decreased with increasing moisture content (cf. FIG. 5).
EP A 474.705 of Starch Australia Ltd. discloses a process for the manufacture of films, said films having a good mechanical strength and good stretchability. The films are produced from a granulate made from starch having a high amylose content, preferably at least 50 wt. %, in an extruder equipped with a flat die wherein during the extrusion process water is removed by applying a vacuum. Removal of water is said to be beneficial as it would provide a thermoplastic material unknown from the prior art which is compatible with polymer films and which can be co-extruded with other polymers, e.g. polypropylene. EP A 495.056 of Cerestar Holding B.V. relates to a similar process for making a film wherein “superdry” starch, i.e. starch containing less than 8 wt. % water, is employed. In particular, EP A 495.056 discloses a process for extruding or injection moulding starch containing compositions, said process providing substantially transparent products, provided that the starch used contains less than 8% by weight of water, that the water content of the starch in the barrel of the extruder or injection moulding machine is controlled so it is within the range of 5 to 20% by weight (based on the weight of the starch) and that water is removed from the composition immediately before the composition leaves the barrel of the extruder or the injection moulding machine so that the water content of the composition passing through the die and/or entering the mould is less than 3% by weight of the starch.
EP A 774.975 of Van De Wijdeven discloses that the preparation of fully destructurised starch and the manufacture of shaped articles such as implants that are made of the fully destructurised starch, optionally in the form of a granulate, can be made by processes conducted by the methods disclosed in either EP A 282.451, GB 2.190.093 or EP A 304.401. However, it is preferred that the technique employed comprises an extrusion step followed by an injection moulding step as is disclosed in EP A 304.401 wherein it is of utmost importance that by variation of pressure, temperature, residence time, amount of water and the like a shaped article such as an implant is provided that is not toxic and degradable in vivo to a vertebrate, e.g. a mammal. It is furthermore preferred that a starch essentially free from amylose, e.g. waxy maize starch, is used as starting material for the preparation of the granulate. Example 1 of EP A 774.975 discloses the preparation of a granulate of fully destructurised starch by extruding commercially available, pure native starch, optionally in the presence of biocompatible additives, at a pressure of 15 MPa and 160° C. according to the method disclosed in EP A 282.451 (which employs an inorganic acid as a chain scission catalyst) and EP A 304.401 (which does not employ a chain scission catalyst). Example 2 of EP A 774.975 discloses the manufacture of bullet shaped implants from the granulate as obtained in Example 1, wherein the method according to EP A 282.451 or EP A 304.401 is employed. Consequently, the granulate and the bullet shaped articles according to EP A 774.975 are different from those of the present invention.
EP A 994.654 of Aventis Res. & Tech. & Co. discloses a thermoplastic mixture that can be used to manufacture e.g. hollow solid shaped articles. The thermoplastic mixture comprises starch and a polyhydroxy carboxylic acid derived from an aldose or a ketose as a plasticizer or a lactone of said polyhydroxy carboxylic acids.
The use of starch based compositions for producing other materials and products is well known in the art. For example, film materials and fibres are disclosed in EP A 474.705, EP A 495.056, EP A 560.014, EP A 1.035.163 and EP A 1.103.254. Expanded products based on starch derived materials are for example disclosed in EP A 376.201, EP A 544.234, EP A 712.883 and EP A 1.064.330. However, such expanded products have a relatively low bulk density, e.g. 1.6 to 80 kg/m3 (cf. EP A 376.201) and are often used for packaging applications. The use of mixtures of starch and synthetic polymers for all kind of purposes is also well known in the art. Reference is for example made to EP A 327.505, EP A 413.798, EP A 400.532, EP A 436.698, EP A 437.561, EP A 437.589, EP A 494.287, EP A 539.541, EP A 575.349, EP A 519.367, EP A 522.358, EP A 560.244, EP A 670.683, EP A 679.172, EP A 682.070, EP A 711.326, EP A 775.171, EP A 819.147, EP A 1.282.662 and U.S. Pat. No. 6,821,538. However, products based on such mixtures have inter alia a poor biodegradability and are suspicious regarding (cyto)toxicity and suitability for implantation
The biodegradable materials produced by the methods according to the prior art have several disadvantages. For example, many methods employ additives such as plasticizers that are not of natural origin and are undesired in biodegradable materials intended for e.g. human applications. Such additives are in particular undesired as they may give rise to inflammation and other adverse effects such as the formation of granulomas when shaped articles made of these biodegradable materials come in contact with living tissue. Additives such as lubricants and extenders are also commonly used which may cause similar undesired effects. Many methods also employ other sources of starch besides native starch, e.g. (chemically) modified starch, starch derivatives, combinations with hydrophilic (synthetic) polymer compositions (cf. for example EP A 110.824), and the like.
The prior art has also not acknowledged processing factors such as pressure, temperature and residence time, in particular in relation to mechanical properties, (cyto)toxicity properties and in vitro and in vivo degradability of the biodegradable material and of the shaped articles manufactured from the biodegradable material.